Color changing matrix as wear indicator

ABSTRACT

A sustained-release matrix for dental application includes either an anti-microbial agent or a colorant that is released from the matrix when the matrix contacts water. The preferred matrices include a water-soluble polymer and a water-insoluble support resin.

This is a continuation of application Ser. No. 08/467,556, filed Jun. 6,1995, now issued as U.S. Pat. No. 5,723,132, which is a divisional ofSer. No. 08/262,961, filed Jun. 21, 1994, which is a divisional of Ser.No. 07/898,471, filed Jun. 15, 1992, now issued as U.S. Pat. No.5,340,581.

BACKGROUND OF THE INVENTION

The invention relates to sustained-release matrices.

Most humans suffer from tooth decay and/or periodontal disease caused bybacteria in the mouth. As a result, decreasing the number of bacteria inthe mouth has long been the target of persons working in the health carefield. The most common way of minimizing the number of bacteria is tobrush and floss the teeth regularly, and to visit a dental hygienist tohave the teeth and gums cleaned thoroughly. Another prior approach isoral rinsing, including with a solution containing a knownanti-microbial agent like chlorhexidine digluconate.

After a toothbrush has been used, there are a large number of bacteriaclinging to the bristles, even after the brush has been rinsed. This, ofcourse, is undesirable, and these bacteria typically will multiply onthe bristles between uses. To counter this problem, self-sterilizingtoothbrushes have been described in the prior art. One suchself-sterilizing toothbrush is described by White et al., U.S. Pat. No.2,216,333, and includes a combination of a water soluble salt (e.g.,sodium carbonate) with an anti-microbial agent (e.g., sulfur). The twoare fused to a solid hard body and attached to the head of thetoothbrush at the base of the bristles. When exposed to water the sodiumcarbonate dissolves, forming an alkaline solution that in turn dissolvessome sulfur, which kills bacteria.

Toothbrushes wear out with extended use. Breuer et al., U.S. Pat. No.4,802,255, describe a toothbrush that includes filaments that release adye, and thus change color, in response to increased use of thefilament. The change in color provides a means for monitoring the degreeof wear of the toothbrush.

Kent, U.S. Pat. No, 5,061,106, describes including capsules ormicrospheres in the tuft holes in which the bristles of a toothbrush aremounted. The capsules or microspheres include a disinfectant or medicantthat is released during use. A dye may also be included in thestructures. The dye also is released over time to enable the user tobecome aware of when the contents of the capsules are depleted.

SUMMARY OF THE INVENTION

The invention features sustained-release matrices that are particularlysuited for use with toothbrushes. The matrices can include ananti-microbial agent that is released over time when the matrices areexposed to water. The matrices may also include a colorant and awater-leachable substance that is released over time when the matricesare exposed to water to cause the matrix to change color.

In one aspect the invention features an oral brush that includes asustained-release matrix made from a support resin, a water-solublesubstance (preferably a water-soluble polymer), and an anti-microbialagent. When the matrix contacts water, the water-soluble substancedissolves, causing the release of the anti-microbial agent.

An oral brush, as used herein, is any brush that includes a handle and ahead attached to a brush designed for insertion into the mouth. Thebrush portion preferably is made from the common bristles found intoothbrushes, but can also be designed for massaging the gums ratherthan the teeth. For example, Kaminski et al., U.S. Ser. No. 07/724,129,which was filed on Jul. 1, 1991, is assigned to the same assignee as thepresent application and is hereby incorporated by reference, describesan interdental foam brush in which the brush portion is made of a softpolyurethane foam.

A support resin, as used herein, is an essentially water-insolublepolymer that provides structural integrity to the matrix as the othercomponents of the matrix--the water-soluble polymer and anti-microbialagent--dissolve or leach out. A further description of what constitutesa support resin is included in the Other Embodiments section.Preferably, the polymer used as the support resin should a have a lowprocessing temperature (less than 130° C.) so that it can be readilycombined with anti-microbial agents that are unstable at hightemperature. Also, the polymer should not become brittle as the othercomponents dissolve or leach out, so that the matrix does not breakapart readily when handled.

Preferred polymers for the support resin include polystyrene,polyurethane, ethylene vinyl acetate, polyethylene, styrene/rubber, andethylene/propylene. The more preferred support resin is an ethylenevinyl acetate polymer. Most preferably the ethylene vinyl acetatepolymer includes between 5% and 50% vinyl acetate, and has a softeningpoint of between 100° C. and 35° C., respectively.

A water-soluble substance, as used herein, is a substance that issufficiently soluble in water that it will dissolve out of the matrixduring contact with water to form channels in the matrix through whichthe anti-microbial agent will leach into the water. A furtherdescription of what constitutes a water-soluble substance is provided inthe Other Embodiments section.

The preferred water-soluble substances are polymers. The preferredpolymers are starches, polyvinyl alcohols, polyethylene oxides,hydroxyalkyl starches, hydroxyethyl and hydroxypropyl celluloses, andgelatins. The most preferred are polyethylene oxides, most preferably aPolyox having a molecular weight of between 100,000 and 5,000,000.

An anti-microbial agent is a substance that kills bacteria. Thepreferred anti-microbial agent for use in the matrix is chlorhexidine,most preferably the digluconate salt thereof; the hydrochloride anddiacetate salts of chlorhexidine can also be used. Other anti-microbialagents that can be included in the matrix include tetracycline (andother antibiotics), and domiphen bromide.

Preferably, the matrix is a flat template having a thickness of up to 4mm and is attached to the head of the body at the base of the bristles.The preferred templates have a surface area of at least 0.01 in², morepreferably at least about 0.1 in². Most preferably, the template has thesame surface area as the toothbrush head (minus the bristles). In thisposition the template is exposed to water when the brush is rinsed andto saliva when it is inserted into the mouth, and can supply theanti-microbial agent to the bristles for self-sterilization and to themouth to kill bacteria. The matrix can also be attached to any otherpart of the brush (e.g., the back of the brush head or at the junctionof the brush head and handle), provided that the part of the brush it isattached to is sufficiently close to the head end that it typically isinserted into the mouth during use.

In other preferred embodiments, the matrix includes two layers, joinedtogether. By "two layers", it is meant that one section of the templatehas a different composition than a second section. The first outer layerincludes a support resin or a water-soluble polymer, and ananti-microbial agent; the second inner layer includes the support resin.Significantly, the first layer can include a large quantity ofanti-microbial agent because the layer includes less (or none) of thesupport resin, yet the layer is stable because the co-extruded secondlayer provides the necessary support. The second layer may also include,optionally, some water-soluble polymer and/or anti-microbial agent.

The invention features, in another aspect, an oral brush that includes atemplate including a water-soluble polymer and an anti-microbial agent.

The invention features, in another aspect, a matrix including ethylenevinyl acetate, polyethylene oxide, and an anti-microbial agent such aschlorhexidine. The matrix can be sized, shaped, and otherwise designedfor short or long term placement at some point in the mouth. The matrixcan also be designed as a template for inclusion on a toothbrush, or canbe used to coat dental floss, or other dental instrument(s).

The matrices of the invention provide a controlled release of ananti-microbial agent into the mouth. When included on a toothbrush, thematrix repeatedly supplies controlled dosages of the agent to killbacteria in the mouth and on the bristles of the brush. The matrices areeasy to manufacture, and their composition, shape and thickness can beadjusted to provide the best properties for the intended use. Forexample, the amount and type of polyethylene oxide in the preferredembodiment can be modified so that the viscosity of the released polymerin solution is less than the viscosity of the saliva in the mouth.

Another aspect of the invention features a wear-indicator oral brushthat includes a matrix containing a colorant (e.g., a dye) and awater-leachable substance that is released from the matrix when the oralbrush is used to cause the matrix to change color after repeated (atleast 5) typical uses. The preferred matrix is a template that includestwo co-extruded or co-molded layers. The outer layer, which contactswater and saliva during brushing, preferably includes thewater-leachable substance, which can be, for example, a water-solublepolymer like polyethylene oxide, or the colorant itself, or acombination of the two. The second, inner, layer preferably includes asupport resin, and can also include a colorant (e.g, TiO₂) that providesthe template with a different color, or shade of color, than thecolorant included in the outer layer. The first layer preferably alsoincludes a support resin, although less than the amount included in thesecond layer, and also can include an anti-microbial agent.

The oral brushes having a matrix including a colorant, i.e., pigment ordye, provide a means to monitor the degree of wear of the brush. Wherethe water-leachable substance includes the colorant, over time as thebrush is used the colorant is released, causing the matrix to changecolor. In those embodiments in which the colorant is not water-leachableand thus is not released from the matrix, typically the portion of thetemplate including a water-leachable substance dissolves away throughrepeated use of the brush to expose the section of the matrix thatincludes the colorant, providing an indication of wear. The amounts andtypes of colorant in the matrix can be adjusted so that the color of thematrix changes after the number of uses through which a typical brushshould be used. When the colored matrix also includes an anti-microbialagent, the change of colorant can be designed to correspond with thedepletion of the agent in the matrix.

Other features and advantages of the invention will be apparent from thedescription of the preferred embodiment thereof, and from the claims.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a perspective view of the preferred toothbrush.

FIGS. 2a-2e provide perspective views of some alternative two-layertemplates. FIG. 2f is a cross-sectional view of the template of FIG. 2e,taken along line A--A. In these figures the holes through which thebristles would be inserted are not shown.

DESCRIPTION OF THE PREFERRED EMBODIMENT

Referring to FIG. 1 a toothbrush 10 includes a plastic body having ahandle 12 and a head 14 attached to a bristle portion 16. Also attachedto the head at the base of the bristles is template 20, asustained-release matrix.

The body of the toothbrush is formed by conventional methods well-knownin the art. The handle is shaped to be grasped by a hand, butalternatively can be shaped to fit into an electric toothbrush. Theconfiguration of the head can vary and may be oval, convex curved, flattrim, or serrated V, or any other desired configuration. The shape andsize of handle 12 and head 14 can vary and the axes of the handle andhead may be on the same or a different plane. The bristle portion isformed of tufts of individual filaments attached to the head in mannersknown to the art. Preferred filaments are those formed of polyamide andpolyester. The filaments preferably have substantially uniformlongitudinal lengths of between 0.3 and 6 cm, and substantially uniformcross-sectional dimensions between about 110 to about 350 microns.

There are three types of preferred templates.

1. Single-layer template including chlorhexidine

The single-layer template consists of a resin, ethylene vinyl acetate; awater-soluble polymer, Polyox; and an anti-microbial agent,chlorhexidine digluconate.

Ethylene vinyl acetate is the backbone of the matrix and has negligiblesolubility in water. It provides the matrix with its structuralintegrity when the other components of the matrix leach out during use.Ethylene vinyl acetate has low toxicity and grades are available thathave low processing temperatures. Importantly, ethylene vinyl acetatemaintains the integrity of the matrix without becoming stiff andbrittle.

A sufficient amount, preferably greater than 50 percent by weight, ofethylene vinyl acetate should be included in the matrix so that when theother components leach out there is still enough resin present tomaintain the structure of the matrix. Of course, not so much should beincluded that the matrix cannot be loaded with a sufficient amount ofthe water-soluble polymer and anti-microbial agent; preferably, thematrix should include less than 90 percent of the ethylene vinyl acetateby weight.

The ethylene vinyl acetate polymer used in the matrix preferably shouldcontain between 5 percent and 50 percent by weight vinyl acetate. If thepolymer includes too little vinyl acetate, the matrix may be too stiffand require higher processing temperatures. If the polymer includes toomuch vinyl acetate, the matrix may be rubber-like and too soft toprocess.

Polyox water-soluble resins are non-ionic ethylene oxide homopolymersthat range in molecular weight from about 100,000 and 5,000,000. Polyoxhas a very low degree of toxicity, and grades are available that have alow processing temperature, and are completely water soluble in cold andwarm water.

The preferred Polyox, available from DuPont, is WSR N-750, which has amolecular weight of 300,000. WSR N-750 has a water solubility that issufficient to provide a controlled-release of the anti-microbial agentfrom the matrix at bactericidal levels, but the solubility in the matrixis low enough that it dissolves out slowly, over a period of many uses.

The matrix preferably contains between 5 percent and 40 percent PolyoxWSR N-750 by weight. If too much Polyox is included, the anti-microbialagent may leach out too quickly, and the structural integrity of thematrix once most of the Polyox has leached out may be adverselyaffected. If too little Polyox is included, too low a quantity of theanti-microbial agent may be released from the matrix during use.

The preferred anti-microbial agent is chlorhexidine digluconate, whichis well-known for its gingivitis-prevention properties. The amount ofchlorhexidine included in the matrix depends on the level of the desireddosage and amount of Polyox; preferably, the matrix includes between 1percent and 30 percent of chlorhexidine digluconate by weight. If toohigh a level of chlorhexidine is included, the matrix may becomebrittle. Of course, a sufficient amount of the agent should be includedso that enough is released during use to be effective.

The template should be formed to fit to the shape of the head at thebase of the bristles, and should be as thick as possible to allow formany uses before all of the anti-microbial agent is leached out.Preferably, the template is at least 0.5 mm thick to ensure adequatemechanical strength, and can be up to at least 4 mm thick.

In use, the toothbrush is rinsed with water, toothpaste applied, andthen the head of the brush is inserted into the mouth to brush the teethwith the bristles. Upon contact with water some of the anti-microbialagent diffuses out of the matrix, onto and down the bristles, andeventually into the saliva of the mouth, killing bacteria on contact. Asthe Polyox slowly dissolves with repeated uses of the brush, water isallowed to penetrate into the matrix, making more of the anti-microbialagent accessible by diffusion from the matrix core. Eventually, all ofthe Polyox and agent have left the matrix, and the toothbrush isdiscarded.

The matrix is designed to incorporate the desired criteria of releaserate, dosage, and effective template lifetime by adjusting the thicknessof the template included on the brush, the quantity of anti-microbialagent contained in the matrix, and the quantity of Polyox, or otherwater-soluble polymer, included in the matrix. The higher the desireddosage, the greater the quantity of water-soluble polymer and agentincluded in the matrix. Also, to increase the released dosage, a morewater-soluble form of Polyox can be employed. The lifetime of a givenmatrix can be increased by increasing the thickness of the template.

Examples of preferred matrices were made by the following procedure.

Materials

a. Chlorhexidine dialuconate

A 20 percent solution of chlorhexidine digluconate, available from PlivaPharmaceutical, Chemical, Food, and Cosmetic Industry of Zagreb,Yugoslavia, or ICI, was freeze-dried as follows:

1. Measure 500 ml of chlorhexidine digluconate in a graduated cylinderand transfer it to a 1 liter flask.

2. Adjust volume to 1 liter with double distilled filtered water and mixtogether.

3. Transfer 300 ml. portions of mixture to glass evaporating dishes (8inch diameter).

4. Place all evaporating dishes in the freeze-drying apparatus until allwater is removed.

5. Transfer the chlorhexidine freeze-dried powder to a 1 liter glassbottle and cap.

6. Store the bottle in a refrigerator or a dark room at approximately 4°C.

b. Ethylene Vinyl Acetate

The most preferred ethylene vinyl acetate is sold by DuPont under thetradename ELVAX 360, and has a vinyl acetate content of 25 percent byweight; a tensile strength of 18.0 Mpa at 23° C. (ASTM D638); anelongation of 800 percent at 23° C. (ASTM D638); a softening temperatureof 53° C. (ASTM D1525); and a flexural modulus of 26 Mpa at 23° C. (ASTMD790). ELVAX 360 contains 500 ppm BHT as an anti-oxidant.

In order to mix with chlorhexidine and Polyox powders, ELVAX 360 pelletsare ground into powders with particle sizes of less than 250 micronswith a Glen Mill Granulator (Model #CS 150/100-2) installed with ascreen plate having 1 mm screen holes. A suction system is added to thegrinding chamber to facilitate the removal of powders from the chamberto a container. During grinding, the material is recycled through thegrinder as many times as necessary (usually two or three passes) to meetthe size requirement. A sieve shaker manufactured by the W. S. Tyler Co.is used to control the sizes as needed.

c. Polyox

Polyox WSR N-750 is available from Union Carbide, and has a meltingpoint of 62-67° C. and a molecular weight of 300,000. The Polyox is usedas received and mixed with other components to form the template.

d. Blending of Materials

The ELVAX 360, Polyox, and chlorhexidine digluconate are mixed in ablender. Each component is first weighed and then poured into a glassjar with a capacity of 0.5 kilograms. The jar is then placed on aball-mill rotator and mixed for approximately 1/2 hour. For a quantitygreater than 0.5 kilograms, a V-blender manufactured by Patterson-KellyCo. Inc. is used. The blended material should be stored in a dry, coolroom.

e. Processing

The conventional equipment used to produce the matrix includes anextruder, a cooling plate, and a puller. An extrusion die with anopening of 2" wide is used. To control the thickness of the template,the die utilizes a flexible lip design which enables the die lip to beadjusted anywhere from 0.15" to 0.45". Each die is supplied with asensor for the recording of melt pressure and temperature. Pulling speedare adjusted to produce a 1" wide strip with a thickness of 0.020" or0.040". The strip can then be fabricated into templates.

Samples were made with both a twin-screw and single-screw extruder. TheWerner & Pfleiderer 30 mm twin-screw extruder is based on a corotatingand intermeshing twin-screw system. To minimize Polyox and chlorhexidinedegradation during processing, the twin screws consists of only twohigh-shear kneading elements and the rest being low-shear conveyingscrew elements; the screw speed and processing temperatures are reducedto a minimum. The mixture is fed using a K-Tron twin-screw feeder (ModelT20).

Alternatively, a Haake 3/4 inches single-screw extruder equipped with a5 HP drive motor is employed. When making the most preferred matrix, theextruder was operated with a screw speed of 35 rpm, a barrel pressure of70 psi, a die pressure of 80 psi, barrel temperature of 113° C., and adie temperature of 113° C.

The blend of materials is fed to either extruder and the strip producedis pulled onto a plate by a Farris puller at a speed of between three orfour feet per minute with minimum tension on the strip. The strip iscooled on a plate placed inside a PVC tube by blowing dry compressed airinto the tube at approximately 10 CFM. The finished product should bekept in a cool, dry room.

The matrices can also be made by other conventional processes, such asby injection molding, casting foam dispensing machines, and reactioninjection molding. In addition, two color injection molding can be usedto make the toothbrush/matrix combination.

Toothbrush Preparation

Toothbrushes including the sustained-release matrix were preparedaccording to the following procedure:

1. Toothbrush handles with undercuts on the toothbrush head for placingtemplates were molded.

2. The strips prepared above were cut into two strips having maximumwidth of 39/64". Tape was used to hold the material to preventstretching.

3. Sets of holes corresponding to the desired bristle pattern to be usedwith the brush were punched with a Dake arbor press.

4. Templates of the desired size were cut from the strips, and glued tothe head of the toothbrush body.

5. The bristles were attached to the head by standard procedures.

Testing for Sustained-Release Properties

The sustained-release matrices of the invention can be tested for theirlong-term release profiles according to the following procedure.

First, a calibration plot of chlorhexidine digluconate in distilledwater was prepared over concentration range of 2 to 40 mcg/ml. Releasestudies were performed in triplicate; the procedure is summarized below:

1. Samples (1/2"×1") were cut from the strip by random sampling.

2. The samples were placed in 250 ml beakers, which were then set into ashaking water bath (37° C., 80 rpm).

3. 5 ml of distilled water were pipetted to each beaker.

4. After 5 minutes, the samples were removed from beakers and assayedfor chlorhexidine content in release solution by uv-spectrophotometricanalysis.

5. This procedure was repeated for 100 release periods.

The preferred strips showed excellent chlorhexidine releasecharacteristics over extended periods of use. The composition of thepreferred strips, and their release properties after 100 uses, aresummarized in the Table below. In the Table, EVA is the preferredethylene vinyl acetate discussed above; the Polyox is either the morepreferred WSR N-750, or a 60:40 blend (60% Polyox coagulant grade, 40%WSR N-750 from Union Carbide); CHG is chlorhexidine digluconate; "S"means the template was prepared by single-screw extrusion, "T" bytwin-screw extrusion; CHG! (ppm) is the concentration of CHG in ppm inthe release solution at 100 releases and 60 m (60 mesh) or 18 m (18mesh) is the particle size of chlorhexidine digluconate employed (noparticle size listing indicates that the chlorhexidine was not sievedfollowing freeze-drying). All of the templates were still releasing over1 ppm chlorhexidine after 100 uses. The most preferred matrix is 2 mmthick and includes 60% EVA, 15% Polyox WSR N-750, and 25% chlorhexidinedigluconate.

    ______________________________________    Thickness           Composition (%)            CHG!    (mm)   EVA    Polyox     CHG             (ppm)    ______________________________________    1.0    70     15     (60:40)                               15   ICI     S    5.51    1.0    65     15     (60:40)                               20   ICI     S    6.49    1.0    70     15     (N-750)                               15   ICI     S    20.98    0.5    70     15     (60:40)                               15   ICI     S    1.32    0.5    70     15     (N-750)                               15   ICI     S    1.57    0.5    70     15     (N-750)                               15   ICI     S    2.19    0.5    70     15     (N-750)                               15   ICI     S    2.53    1.0    65     20     (N-750)                               15   ICI     S    8.63    1.0    60     25     (N-750)                               15   ICI     S    12.41    1.0    50     35     (N-750)                               15   ICI     S    7.04    1.0    70     15     (N-750)                               15   ICI     T    7.84    1.0    70     15     (N-750)                               15   ICI     T    23.15    1.0    70     15     (N-750)                               15   ICI     T    2.73    1.0    70     10     (N-750)                               20   ICI     T    21.38    2.0    65     15     (N-750)                               20   (60 m ICI)                                            S    17.59    2.0    70     15     (N-750)                               15   (Pliva) S    12.43    2.0    65     20     (N-750)                               15   (60 m ICI)                                            S    7.62    2.0    70     15     (N-750)                               15   (60 m ICI)                                            S    11.20    2.0    70     15     (N-750)                               15   (18 m ICI)                                            S    6.78    2.0    70     15     (N-750)                               15   (60 m ICI)                                            T    9.10    2.0    65     20     (N-750)                               15   (60 m ICI)                                            T    9.08    2.0    70     15     (N-750)                               15   (Pliva) T    1.53    2.0    60     15     (N-750)                               25   (60 m ICI)                                            T    50.76    2.0    65     15     (N-750)                               20   (60 m ICI)                                            T    7.67    2.0    60     15     (N-750)                               25   (60 m Pliva)                                            T    9.83    2.0    55     15     (N-750)                               30   (60 m Pliva)                                            T    7.10    2.0    60     15     (N-750)                               25   (60 m ICI)                                            S    63.00    2.0    55     10     (N-750)                               35   (60 m Pliva)                                            T    15.78    2.0    60     15     (N-750)                               25   (18 m ICI)                                            S    62.34    2.0    60     15     (N-750)                               25   (60 m Pliva) 47.22    2.0    60     15     (N-750)                               25   (Pliva) S    72.63    2.0    60     15     (N-750)                               25   (Pliva) T    29.72    2.0    60     15     (N-750)                               25   (ICI)   S    54.56    2.0    60     15     (N-750)                               25   (ICI)   T    31.37    2.0    60     15     (N-750)                               25   (60 m Pliva)                                            S    61.24    2.0    60     15     (N-750)                               25   (60 m Pliva)                                            S    60.03    2.0    60     15     (N-750)                               25   (60 m Pliva)                                            S    60.43    ______________________________________

2. Two-layer template including chlorhexidine

The preferred single-layer template generally includes over 50% supportresin (EVA) by weight to achieve good mechanical properties andprocessibility. This, to some extent, limits the quantity ofchlorhexidine that can be included in the matrix. An alternativetwo-layer template provides a higher quantity of chlorhexidine in theportion of the template that primarily contacts water and saliva. Thefirst, outer layer contains less ethylene vinyl acetate and morepolyethylene oxide and chlorhexidine. The second, inner layer has thecomposition of the preferred single-layer embodiment, although thesecond layer could consist entirely of ethylene vinyl acetate. Apreferred two-layer matrix includes 65% ethylene vinyl acetate, 15%Polyox, and 20% chlorhexidine digluconate in the inner layer, and 30%ethylene vinyl acetate, 25% Polyox, and 45% chlorhexidine digluconate inthe outer layer. The inner layer should include at least 60% of thesupport resin; the outer layer can include upwards of 50% chlorhexidine.

The outer layer releases a higher dosage of chlorhexidine when contactedwith water, yet has good strength and processibility because the secondlayer provides the necessary support. As the outer layer wears away, theanti-microbial agent in the inner layer also is released. The outerlayer preferably is 0.25 to 3 mm thick, while the inner layer preferablyis 0.1 to 0.5 mm thick.

The two-layer templates can be produced either by conventionalco-extrusion or co-injection molding techniques, from two differentmixtures. Alternatively one layer can be extruded and then the otherlayer can be thermoformed/compression molded or laminated onto theextruded layer.

An alternative two-layer embodiment has an outer layer consisting onlyof the support resin and the anti-microbial agent. The preferredanti-microbial agent, chlorhexidene digluconate, is water-soluble,although not to the same degree as the water-soluble polyethylene oxide.Because the outer layer includes a high quantity of the anti-microbialagent, enough of the agent can dissolve out of the matrix to provide asufficient dosage of the agent without the assistance of a water-solublepolymer.

3. Template including a colorant

The wear-indicator template preferably includes two layers, each with adifferent colorant. The outer layer includes a water-soluble polymer(preferably polyethylene oxide, polyethylene glycol, or polyvinylalcohol) and a colorant, preferably a water-leachable colorant; asupport resin is optional. The inner layer includes a support resin anda second colorant, like titanium dioxide, which provides a solid whiteappearance. The different colorants should be selected to provide aclear contrast so that a user can plainly discern the color change asthe colorant in the outer layer leaches out over time.

The two-layer templates including a colorant can be produced by the sametechniques used to produce the two-layer templates including ananti-microbial agent discussed above.

The preferred wear-indicating template is illustrated in FIG. 2a andconsists of an outer layer 22, which includes the colorant that isreleased during use, and an inner layer 24, which is adjacent thetoothbrush during use. Inner layer 24 includes titanium dioxide.

Alternative two-layer template embodiments are illustrated in FIGS.2b-2f. In these embodiments, no colorant is included in the outer layer26 and a non-white colorant is included in the inner layer 28. The outerlayer in these embodiments preferably consists only of water-solublepolymer; as the outer layer dissolves away during use the colorant inthe second layer becomes visible, or more visible, providing anindication of the degree of wear of the brush.

Referring to FIG. 2b, a template has a flat outer layer 26 and a flatinner layer 28 that are approximately the same size. As outer layer 26dissolves away with repeated use, a colorant in inner layer 28 becomesvisible to a user looking straight down at the surface of the bristlesthat contact the teeth.

Referring to FIG. 2c, inner layer 28 of a template has elements 30 thatextend into grooves in outer layer 26. As outer layer 26 dissolves away,elements 30, which include colorant, become visible to the user asstripes at the base of the bristles. A similar embodiment is illustratedin FIG. 2d, except that elements 32 extend along the exterior of outerlayer 26. In this embodiment, as outer layer 26 dissolves away a coloredstrip along the edge of the template becomes visible to a user lookingstraight down at the surface of the bristles that contact the teeth.

Referring to FIGS. 2e and 2f, an alternative template includes an innerlayer 28 that is fully surrounded by the outer layer 26 except atsurface 34, where the template is attached to the head of the brush. Asouter layer 26 dissolves, inner layer 28 becomes visible from the sidesand from the top.

Although not illustrated, other alternative matrices include those inwhich the inner layer(s) is simply two narrow strips, like elements 30;and those in which the inner layer includes cyclindrical elements thatextend upwards from the inner layer into the outer layer. In the latterembodiment, as the outer layer dissolves away the inner layer becomesvisible as colored dots.

The following examples were made from two 3/4 inch extruders with aco-extrusion die to produce two-layer templates having the design shownin FIG. 2a and having a thickness of about 10 mm.

Example A

The first layer of the template consisted of 44.6% ethylene vinylacetate (Elvax 360), 44.5% Polyox N-750, 10% polyethylene glycol(Dow-E4500), and 0.9% of a dark blue pigment (FD&C Blue No. 2, AluminumLube 35-42%, available from Warner Jenkinson of St. Louis, Mo.). Thesecond layer consisted of 99.5% Elvax 360 and 0.5% titanium dioxide.When the template was submerged in water for 24-hours, the initial darkblue color changed to a light blue.

Example B

The first layer of the template includes 49.5% Elvax 360, 49.5% PolyoxN-750, and 1% dark blue pigment. The second layer was the same as inExample A. The results of a 24-hour water-submerge test also were thesame.

Example C

The first layer of the template consists of 99% polyvinyl alcohol and 1%of the dark blue pigment, and no support resin. The second layer was thesame as for the other two examples. When this template was subjected toa 24-hour water-submerge test, the initial dark blue color of thetemplate turned to white.

Other Embodiments

Other embodiments are within the claims. For example, otherwater-insoluble polymers can be used as the support resin. To determinewhether a polymer can be used as a support resin within the meaning ofthis application, a template should be prepared containing 60% of thepolymer, 15% Polyox WSR N-750, and 25% chlorhexidine digluconate. Matrixsamples (1/2"×1") having a thickness of 2 mm are placed in 250 mlbeakers which are then set into a shaking water bath (37° C., 80 rpm)for 8 hours. If the matrix has maintained its structural integrity inthe bath and does not fall apart, the polymer is a support resin.Examples of the specific polymers that can be used in place of EVA asthe support resins include Hytrel G-4074 (a polyester available fromDuPont); Hytrel 4056 (a polyester elastomer also available from DuPont);Vestenamer 8012 (TPE, available from Huls America); Rimplast PSW 2159 (asilicone, available from Petrarch Systems); Prolytropes (anethylene/propylene alloy available from A. Schulman, Inc.); Millathanes(a polyester urethane available from Millathane); Kraton G-7680 (astyrene/rubber available from Shell Chemical); and Santoprene 101-55 (apolyolefin alloy available from Monsanto Chemical). Prolytropes andKraton G-7680 are more preferred because of their relatively lowprocessing temperatures, 29° C. and 57° C., respectively. Examples ofother general classes of polymers that can be used as support resinsinclude polyurethanes, polycarbonates, polyesters, polyethylenes,polypropylenes, polystyrenes, and polyvinyl chloride; polyurethanes,polyethylenes, and polystyrenes are more preferred because forms ofthese polymers with relatively low processing temperatures areavailable.

Additionally, other water-soluble substances can be used in place ofPolyox in the matrix. To determine whether something is a water-solublesubstance within the meaning of this application, a template should beprepared containing 80% EVA and 20% of the substance. Matrix samples(1/2"×1") having a thickness of 2 mm are placed in 250 ml beakers whichare then set into a shaking water bath (37° C., 80 rpm) for 8 hours.After that time, the matrix is removed, and photomicrographs(magnification of 350 X) of the matrix after the procedure are comparedto photomicrographs (350 X) of the matrix prior to the procedure. Ifafter the procedure channels and pores have formed into the matrix, thesubstance is a water-soluble substance. Other water-soluble naturalpolymers than can be used include agar; carrageenan; corn starch; guargum; gum arabic; gum karaya; gum tragacanth; locust bean gum; potato,wheat and rice starches; tapioca; casein; pectin; and sodium alginate.Modified natural polymers then can be used include cationic starch;dextran; hydroxyalkyl starches; hydroxyethyl and hydroxypropylcellulose; methyl cellulose; sodium carboxymethyl cellulose; xanthangum; gelatin; and sodium carboxymethyl starch. Synthetic polymerssuitable for use include polyvinyl alcohol; cationic resins andquaternary ammonium compounds; poly (N-vinyl-2-pyrrolidinone); vinylether polymers; styrene-maleic anhydride copolymers; ethylene-maleicanhydride copolymer; hydrophilic gels; and polymeric surface-activeagents. Inorganic salts, (e.g., EDTA, NaCl, Na₂ CO₃, and KCl) andfillers may also be used.

Anti-microbial agents that can be used in place of chlorhexidinedigluconate include antibiotics such as actinobolin, chlortetracycline,tetracycline, streptomycin, kanamycin, neomycin, niddamycin, bacitracin,erythromycin, penicillin, rancemycin, gramicidin, saramycin, andpolymyxin B; as well as antiplaque enzymes such as mucinases,pancreatin, fungal enzymes, protease-amylase, dextranase, moimnase,zendium, amyloglucosidase, and glucose oxidase. Other conventionalantimicrobials that can be used include phenolic compounds (e.g.,phenol, thymol, 2-phenylphenol, hexylresorcinol), and listerine (thymol,eucalyptol, menthol, methylsalicylate); bi-pyridines (e.g., octenidene);pyrimidines (e.g., hexetidine); halogens (e.g., iodine, iodophores,fluorides); quaternary ammonium salts (e.g., cetylpyridinium chloride,benzethonium chloride, domiphen bromide); oxygenating agents (e.g.,peroxides; perborate); herbal extracts (e.g., sangnimarine); heavy metalsalts (e.g., silver, mercury, zinc, copper, tin); and otherbis-biguanidines besides chlorhexidine (e.g., alexidine). Of course,other chlorhexidine salts like the diacetate and dihydrochloride can beused in place of chlorhexidine digluconate.

Moreover, the matrices can be used in other ways, for example byimpregnating the bristles of a toothbrush with small matrix particles,by inserting the matrices into the holes the toothbrush head into whichbristles are then inserted, or by coating the matrix on dental floss.The matrix also can be attached to the side of the head of thetoothbrush opposite the side to which the bristles are attached.Alternatively, a matrix can be designed to be inserted and left in themouth for an extended period of time, for example as a small ring thatfits around a tooth.

Templates can be designed that are sustained-release but that do notrelease over 1 ppm chlorhexidine after 100 uses by the test previouslydesigned. For example, a disposable toothbrush, which would be discardedafter only a few uses, does not require such extended release lifetime.For the purposes of this invention, sustained-release means that thematrix still releases at least 1 ppm of the anti-microbial agent after10 uses (more preferably after 50 uses) when tested according to theprocedure described in the Preferred Embodiment section.

Any of the two-layer templates shown in FIG. 2 can be used to providethe sustained-release of an anti-microbial agent.

Further, other well-known, conventional additives such as fillers,binders, lubricants, and channeling agents can be included in thematrix, although care should be taken that these additives do notadversely affect the agent release rate.

I claim:
 1. A color-changing matrix comprising two joined layers, anouter layer comprising a water-soluble polymer, a water-insolublepolymer and a first colorant, and an inner layer comprising awater-insoluble polymer and a second colorant different from said firstcolorant.
 2. The color-changing matrix of claim 1 wherein thewater-soluble polymer comprises polyethylene oxide.
 3. Thecolor-changing matrix of claim 2 wherein the polyethylene oxide has amolecular weight of 100,000 to 5,000,000.
 4. The color-changing matrixof claim 3 wherein the polyethylene oxide is a blend comprising 60 partsof coagulant grade polyethylene oxide and 40 parts of polyethylene oxideof molecular weight 300,000.
 5. The color-changing matrix of claim 2, 3or 4 wherein the water-insoluble polymer in each layer is selected fromthe group consisting of polystyrene, polyurethane, ethylene vinylacetate, polyethylene, styrene/rubber and ethylene/propylene.
 6. Thecolor-changing matrix of claim 1 wherein the inner layer additionallycomprises a water-soluble polymer.
 7. The color-changing matrix of claim6 wherein the water-soluble polymer in each layer comprises polyethyleneoxide.
 8. The color-changing matrix of claim 7 wherein the polyethyleneoxide has a molecular weight of 100,000 to 5,000,000.
 9. Thecolor-changing matrix of claim 8 wherein the polyethylene oxide is ablend comprising 60 parts of coagulant grade polyethylene oxide and 40parts of polyethylene oxide of molecular weight 300,000.
 10. Thecolor-changing matrix of claim 7, 8 or 9 wherein the water-insolublepolymer in each layer is selected from the group consisting ofpolystyrene, polyurethane, ethylene vinyl acetate, polyethylene,styrene/rubber and ethylene/propylene.
 11. The color-changing matrix ofclaim 1, 3, 6 or 8 wherein said two joined layers are coextruded. 12.The color-changing matrix of claim 1, 3, 6 or 8 wherein said outer layeris adapted to dissolve away through repeated contact with water toexpose said inner layer.
 13. A method of indicating wearcomprisingproviding a color-changing matrix comprising two joinedlayers, an outer layer comprising a water-soluble polymer, awater-insoluble polymer and a first colorant, and an inner layercomprising a water-insoluble polymer and a second colorant differentfrom said first colorant, and repeatedly contacting said matrix withwater to expose said inner layer.
 14. The method of claim 13 wherein thewater-soluble polymer comprises polyethylene oxide.
 15. The method ofclaim 13 wherein the polyethylene oxide has a molecular weight of100,000 to 5,000,000.
 16. The method of claim 15 wherein thepolyethylene oxide is a blend comprising 60 parts of coagulant gradepolyethylene oxide and 40 parts of polyethylene oxide of molecularweight 300,000.
 17. The method of claim 14, 15 or 16 wherein thewater-insoluble polymer in each layer is selected from the groupconsisting of polystyrene, polyurethane, ethylene vinyl acetate,polyethylene, styrene/rubber and ethylene/propylene.
 18. The method ofclaim 13 wherein the inner layer additionally comprises a water-solublepolymer.
 19. The method of claim 18 wherein the water-soluble polymer ineach layer comprises polyethylene oxide.
 20. The method of claim 19wherein the polyethylene oxide has a molecular weight of 100,000 to5,000,000.
 21. The method of claim 20 wherein the polyethylene oxide isa blend comprising 60 parts of coagulant grade polyethylene oxide and 40parts of polyethylene oxide of molecular weight 300,000.
 22. The methodof claim 19, 20 or 21 wherein the water-insoluble polymer in each layeris selected from the group consisting of polystyrene, polyurethane,ethylene vinyl acetate, polyethylene, styrene/rubber andethylene/propylene.
 23. The method of claim 13, 15, 18 or 20 whereinsaid two joined layers are coextruded.
 24. The method of claim 13, 15,18 or 20 wherein said outer layer is adapted to dissolve away throughrepeated contact with water to expose said inner layer.